The objective of the research is to define the chemical structure and the biological properties of an endogenous inhibitor of the (Na-K) pump present in human cerebrospinal fluid (CSF). This proposal stems from our observation that a component of human CSF inhibits the active transport of cations in human red cells and the in vitro activity of the enzyme (Na-K) ATPase. This inhibitory substance, possibly a neuropeptide, can be separated by chromatographic techniques, is sensitive to proteolytic digestion and increases after the expansion of the extracellular fluid volume. Specific aims include: 1) Purification and identification of the (Na-K) pump inhibitor of human CSF; 2) Sequence and synthesis of the active molecule(s); 3) Investigation of the mechanism underlying its inhibitory action on the (Na-K) ATPase; 4) Studies on its biological properties; and 5) Development of specific and sensitive tests allowing its detection in body fluids and tissues. These studies should provide new information about the physiological regulation of ion transport across cell membranes. In addition, they may also provide new insights, and possibly new biological tests and pharmacological approaches, to the pathophysiology of ion transport and related diseases.